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Asthana R, Hamandi B, Brnabic A, Papadimitropoulos E, Piquette-Miller M. Meta-analysis and systematic review on Sulfasalazine/5-ASA use during pregnancy: Impact on neonatal and pregnancy outcomes. Reprod Toxicol 2025; 135:108939. [PMID: 40334871 DOI: 10.1016/j.reprotox.2025.108939] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2024] [Revised: 04/15/2025] [Accepted: 05/02/2025] [Indexed: 05/09/2025]
Abstract
OBJECTIVES This study aims to evaluate the risks associated with Sulfasalazine (SSZ) and 5-aminosalicylic acid (5-ASA) use during pregnancy on perinatal outcomes in women with Inflammatory Bowel Diseases (IBD). We compared these outcomes with those of healthy pregnant women and with pregnant women with IBD not on medication. DATA SOURCES We searched Medline, Embase, CINAHL, Scopus, and PubMed databases up to December 27, 2023. We also screened reference lists of identified studies and utilized SCOPUS to find additional relevant research. STUDY ELIGIBILITY CRITERIA We included studies that specifically examined SSZ/5-ASA usage during pregnancy. Our outcomes of interest included congenital malformations, stillbirths, neonatal outcomes, preterm delivery, live births, small for gestational age, and pregnancy loss. SYNTHESIS METHODS Pooled odds ratios (OR) were calculated using a random-effects model to accommodate within-study and between-study variability, given the substantial heterogeneity from differences in study designs and methodologies. The risk of bias was assessed using the Newcastle-Ottawa Scale (NOS). RESULTS Fifteen observational studies with 2,076,932 participants were included. SSZ/5-ASA use during pregnancy was linked to a significant increase in congenital malformations (OR: 1.33, 95 % CI: 1.17-1.50), stillbirths (OR: 5.12, 95 % CI: 2.74-9.57), and preterm delivery (OR: 1.94, 95 % CI: 1.49-2.52) compared to healthy controls. However, no significant risks were found when compared with pregnant women with IBD not on medication. CONCLUSIONS The observed risks appear related to the disease rather than medication, suggesting treatment may mitigate adverse outcomes. Distinguishing between the effects of disease and medication poses ethical challenges in pregnant populations.
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Affiliation(s)
- Rashi Asthana
- Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada
| | - Bassem Hamandi
- Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada; University Health Network (UHN), Toronto, Ontario, Canada
| | | | - Emmanuel Papadimitropoulos
- Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada; Eli Lilly and Company, Canada
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Garvik OS, Jølving LR, Lund K, Friedman S, Nørgård BM. Paternal use of selective serotonin reuptake inhibitors and adverse health outcomes: A nationwide cohort study on 13,547 exposed children. Andrology 2025; 13:259-267. [PMID: 38639021 DOI: 10.1111/andr.13646] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2024] [Revised: 02/29/2024] [Accepted: 03/27/2024] [Indexed: 04/20/2024]
Abstract
BACKGROUND The use of selective serotonin reuptake inhibitors (SSRIs) has increased over time. Several studies indicate that paternal use of medication may adversely affect the developing fetus. Only a few studies have investigated the association between preconceptional paternal exposure to SSRIs and the risks of adverse health outcomes in children. OBJECTIVES This study aimed to assess adverse birth outcomes and adverse early life events in children fathered by men using SSRIs prior to conception. MATERIALS AND METHODS All live-born singleton children born in Denmark from 1997 until 2019 and their parents were included. The exposed cohort comprised all children fathered by men using SSRIs 3 months prior to conception and the unexposed cohort comprised all other children. We estimated the odds ratios for adverse birth outcomes: small for gestational age (SGA), preterm birth, low Apgar score, and major congenital malformations. Furthermore, we estimated the hazard ratios for adverse early life events of infections and hospitalizations within 1 year from birth. We also examined adverse birth outcomes and the adverse early life events according to SSRI subgroups. RESULTS There was a statistically significantly increased odds ratio 1.15 (confidence interval, CI: 1.06-1.23) for preterm birth. No significant results were found for SGA, low Apgar score, and major congenital malformations. The adjusted hazard ratios for hospitalizations and infections were 1.06 (CI: 1.02-1.11) and 1.02 (CI: 0.97-1.07), respectively. There was a statistically significantly increased odds ratio for preterm birth with respect to the SSRI subgroups citalopram and escitalopram, and for hospitalizations with respect to citalopram. DISCUSSION AND CONCLUSION Although the risks of certain adverse birth and adverse early life outcomes were statistically significantly increased, the ratios were small and may have limited clinical importance. Paternal use of SSRI was in general safe in the preconceptual period.
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Affiliation(s)
| | - Line Riis Jølving
- Center for Clinical Epidemiology, Odense University Hospital, Odense, Denmark
- Research Unit of Clinical Epidemiology, Department of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Ken Lund
- Center for Clinical Epidemiology, Odense University Hospital, Odense, Denmark
- Research Unit of Clinical Epidemiology, Department of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Sonia Friedman
- Center for Clinical Epidemiology, Odense University Hospital, Odense, Denmark
- Gastroenterology Division, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts, USA
| | - Bente Mertz Nørgård
- Center for Clinical Epidemiology, Odense University Hospital, Odense, Denmark
- Research Unit of Clinical Epidemiology, Department of Clinical Research, University of Southern Denmark, Odense, Denmark
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Lund K, Garvik OS, Aagaard SM, Jølving LR, Larsen MD, Damkier P, Nørgård BM. Paternal preconception exposure to non-steroid anti-inflammatory drugs or opioids and adverse birth outcomes: A nationwide registry-based cohort study. Andrology 2025; 13:72-81. [PMID: 37941509 DOI: 10.1111/andr.13551] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Revised: 09/13/2023] [Accepted: 10/19/2023] [Indexed: 11/10/2023]
Abstract
BACKGROUND AND AIM Paternal use of analgesics during the time of conception and adverse birth outcomes are poorly studied. We investigated the association between paternal exposure to non-steroid anti-inflammatory drugs and opioids within 3 months before the date of conception and the risk of adverse birth outcomes (preterm birth, small for gestational age, low Apgar score, and major congenital malformations). METHODS We used nationwide data from the Danish health registers. We included information on all singleton live births, and their fathers and mothers from 1997 to 2018. We created two exposed cohorts, children with preconception paternal exposure to (1) non-steroid anti-inflammatory drugs and (2) opioids. The unexposed cohort was children without preconception paternal exposure to non-steroid anti-inflammatory drugs or opioids, and we performed a sub-analysis against paternal use of acetaminophen (paracetamol). We used logistic regression models to estimate the odds ratios of adverse birth outcomes including 95% confidence intervals. RESULTS We identified 1,260,934 children, 45,667 children with paternal exposure to non-steroid anti-inflammatory drugs, 10,086 children with paternal exposure to opioids, and 1,205,181 unexposed children. The adjusted odds ratio for preterm birth was 1.08 (95% confidence interval, 1.03-1.13) after paternal exposure to non-steroid anti-inflammatory drugs and 1.21 (95% confidence interval, 1.08-1.35) after paternal exposure to opioids. The adjusted odds ratio for small for gestational age was 1.09 (95% confidence interval, 1.03-1.17) after paternal exposure to non-steroid anti-inflammatory drugs, and 1.03 (95% confidence interval, 0.88-1.21) after paternal exposure to opioids. We found null-associations for a low Apgar score and major congenital malformations. Estimates were attenuated when compared against paternal paracetamol exposure. CONCLUSIONS Overall, we found null-associations across the comparisons made. Weak associations were found for paternal exposure to non-steroid anti-inflammatory drugs or opioids and preterm birth and small for gestational age, but not with low Apgar score or major congenital malformation. All associations were attenuated when compared against an active comparator of paternal paracetamol exposure. The effect sizes were small and less likely to be of clinical relevance.
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Affiliation(s)
- Ken Lund
- Center for Clinical Epidemiology, Odense University Hospital, Odense, Denmark
- Research Unit of Clinical Epidemiology, Department of Clinical Research, University of Southern Denmark, Odense, Denmark
| | | | - Signe Marie Aagaard
- Center for Clinical Epidemiology, Odense University Hospital, Odense, Denmark
| | - Line Riis Jølving
- Center for Clinical Epidemiology, Odense University Hospital, Odense, Denmark
- Research Unit of Clinical Epidemiology, Department of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Michael Due Larsen
- Center for Clinical Epidemiology, Odense University Hospital, Odense, Denmark
- Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
| | - Per Damkier
- Department of Clinical Pharmacology, Odense University Hospital, Odense, Denmark
- Research Unit of Clinical Pharmacology, Department of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Bente Mertz Nørgård
- Center for Clinical Epidemiology, Odense University Hospital, Odense, Denmark
- Research Unit of Clinical Epidemiology, Department of Clinical Research, University of Southern Denmark, Odense, Denmark
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Caballero-Mateos AM, Quesada-Caballero M, Cañadas-De la Fuente GA, Caballero-Vázquez A, Contreras-Chova F. IBD and Motherhood: A Journey through Conception, Pregnancy and Beyond. J Clin Med 2023; 12:6192. [PMID: 37834837 PMCID: PMC10573266 DOI: 10.3390/jcm12196192] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2023] [Revised: 09/14/2023] [Accepted: 09/19/2023] [Indexed: 10/15/2023] Open
Abstract
Inflammatory Bowel Disease (IBD) presents distinct challenges during pregnancy due to its influence on maternal health and pregnancy outcomes. This literature review aims to dissect the existing scientific evidence on pregnancy in women with IBD and provide evidence-based recommendations for clinical management. A comprehensive search was conducted across scientific databases, selecting clinical studies, systematic reviews, and other pertinent resources. Numerous studies have underscored an increased risk of complications during pregnancy for women with IBD, including preterm birth, low birth weight, neonates small for gestational age, and congenital malformations. Nevertheless, it's evident that proactive disease management before and throughout pregnancy can mitigate these risks. Continuation of IBD treatment during pregnancy and breastfeeding is deemed safe with agents like thiopurines, anti-TNF, vedolizumab, or ustekinumab. However, there's a call for caution when combining treatments due to the heightened risk of severe infections in the first year of life. For small molecules, their use is advised against in both scenarios. Effective disease management, minimizing disease activity, and interdisciplinary care are pivotal in attending to women with IBD. The emphasis is placed on the continual assessment of maternal and infant outcomes and an expressed need for further research to enhance the understanding of the ties between IBD and adverse pregnancy outcomes.
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Brondfield MN, Mahadevan U. Inflammatory bowel disease in pregnancy and breastfeeding. Nat Rev Gastroenterol Hepatol 2023:10.1038/s41575-023-00758-3. [PMID: 37002407 DOI: 10.1038/s41575-023-00758-3] [Citation(s) in RCA: 27] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/20/2023] [Indexed: 06/19/2023]
Abstract
Inflammatory bowel disease (IBD) has a peak age of diagnosis before the age of 35 years. Concerns about infertility, adverse pregnancy outcomes, and heritability of IBD have influenced decision-making for patients of childbearing age and their care providers. The interplay between the complex physiology in pregnancy and IBD can affect placental development, microbiome composition and responses to therapy. Current evidence has shown that effective disease management, including pre-conception counselling, multidisciplinary care and therapeutic agents to minimize disease activity, can improve pregnancy outcomes. This Review outlines the management of IBD in pregnancy and the safety of IBD therapies, including novel agents, with regard to both maternal and fetal health. The vast majority of IBD therapies can be used with low risk during pregnancy and lactation without substantial effects on neonatal outcomes.
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Affiliation(s)
- Max N Brondfield
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA
| | - Uma Mahadevan
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
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Nørgård BM, Fedder J, Jølving LR, Damkier P, Nielsen J. Adverse Birth and Child Outcomes in Children Fathered by Men Treated with Antidiabetics Prior to Conception: A Nationwide Cohort Study. J Clin Med 2022; 11:6595. [PMID: 36362820 PMCID: PMC9654141 DOI: 10.3390/jcm11216595] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2022] [Revised: 11/04/2022] [Accepted: 11/04/2022] [Indexed: 11/10/2023] Open
Abstract
BACKGROUND The safety of fathers' use of antidiabetic drugs in terms of child outcomes is an important clinical question. We aimed to assess the risk of adverse birth and early childhood outcomes after fathers' use of antidiabetics prior to conception. METHODS A nationwide cohort study based on Danish health registries. The study comprised all live born singleton children in Denmark (1997 through 2018). Children were categorized according to fathers' filled prescriptions for antidiabetic drugs three months prior to conception. Exposed cohorts: children born after paternal use of insulin or non-insulin anti-hyperglycemic agents. The unexposed constituted children born by fathers not treated with antidiabetics prior to conception. We examined adverse birth outcomes (preterm birth, small for gestational age (SGA)), and adverse childhood outcomes in the first year of life (major congenital malformations (MCMs), and infections diagnosed at a hospital). RESULTS A total of 1,318,684 children were included. In all, 5527 children were born after paternal use of insulin, 2121 after use of non-insulin anti-hyperglycemic agents, and 1,311,036 were unexposed. After fathers' use of insulin we did not find increased risk of adverse outcomes. After fathers' use of metformin, the adjusted OR of MCMs was 1.40 (95% CI 1.11-1.76). After fathers' use of sulfonylureas, the adjusted OR of SGA was 1.80 (95% CI 1.11-2.93), and for child gastrointestinal infections the adjusted HR was 1.76 (95% CI 1.04-2.99). CONCLUSIONS Fathers' use of insulin was reassuring. Metformin and sulfonylureas were associated with selected adverse outcomes. Our findings suggest an additional 14 MCMs per 1000 fathers exposed to metformin prior to conception. As there is no meaningful supporting biological rationale, these findings should be confirmed in a different population prior to clinical consequences being drawn.
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Affiliation(s)
- Bente Mertz Nørgård
- Center for Clinical Epidemiology, Odense University Hospital, 5000 Odense, Denmark
- Research Unit of Clinical Epidemiology, Department of Clinical Research, University of Southern Denmark, 5000 Odense, Denmark
| | - Jens Fedder
- Centre of Andrology and Fertility Clinic, Odense University Hospital, 5000 Odense, Denmark
- Research Unit of Gynecology and Obstetrics, Department of Clinical Research, University of Southern Denmark, 5000 Odense, Denmark
| | - Line Riis Jølving
- Center for Clinical Epidemiology, Odense University Hospital, 5000 Odense, Denmark
- Research Unit of Clinical Epidemiology, Department of Clinical Research, University of Southern Denmark, 5000 Odense, Denmark
| | - Per Damkier
- Department of Clinical Pharmacology, Odense University Hospital, 5000 Odense, Denmark
- Department of Clinical Research, University of Southern Denmark, 5000 Odense, Denmark
| | - Jan Nielsen
- Center for Clinical Epidemiology, Odense University Hospital, 5000 Odense, Denmark
- Research Unit of Clinical Epidemiology, Department of Clinical Research, University of Southern Denmark, 5000 Odense, Denmark
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Guerrero Vinsard D, Karagozian R, Wakefield DB, Kane SV. Maternal Outcomes and Pregnancy-Related Complications Among Hospitalized Women with Inflammatory Bowel Disease: Report from the National Inpatient Sample. Dig Dis Sci 2022; 67:4295-4302. [PMID: 34406586 DOI: 10.1007/s10620-021-07210-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2021] [Accepted: 08/02/2021] [Indexed: 12/09/2022]
Abstract
BACKGROUND AND AIMS Previous studies have been inconsistent in reporting the risk of pregnancy-related complications in women with IBD. We aimed to investigate the differences in frequencies of pregnancy-related complications requiring hospitalization in women with IBD compared to women without IBD. METHODS We performed a population-based, cross-sectional study using the 2014 USA National Inpatient Sample. Frequencies of ICD-9 codes for pregnancy-related complications in women aged 18-35 years with IBD were compared to women with no IBD controlling for confounders predisposing to pregnancy complications. Adjusted odds ratios were calculated for each outcome. RESULTS A total of 6705 women with IBD and a pregnancy complication were discharged from the hospital in 2014. In multivariate analyses, there was no statistically significant difference between women with and without IBD for: spontaneous abortion, post-abortion complications, ectopic pregnancy, hemorrhage, severe preeclampsia, eclampsia, early labor, polyhydramnios, hyperemesis, missed abortion, mental disorder during pregnancy, and forceps delivery. Women with IBD had significant lower odds for prolonged pregnancy, gestational diabetes, fetal distress, umbilical cord complications, obstetric trauma, mild preeclampsia, and hypertension. There was, however, higher odds for infectious and parasitic complications (OR 1.74, 95% CI 1.42-2.14, p < 0.0001), UTIs (OR 1.65, 95% CI 1.07-2.60, p = 0.02), and anemia (OR 5.26, 95% CI 4.01-6.90, p < 0.0001). CONCLUSIONS In this large population-based analysis, women with IBD had higher odds for certain infections such as UTIs and anemia during pregnancy when compared to women with no IBD. For other pregnancy-related complications, women with IBD had the same or lower odds than women with no IBD. These data are important to share with women with IBD considering pregnancy.
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Affiliation(s)
- Daniela Guerrero Vinsard
- Department of Gastroenterology and Hepatology, Mayo Clinic, 200 1ST St SW, Rochester, MN, 55905, USA.
| | - Raffi Karagozian
- Department of Gastroenterology and Hepatology, Tufts Medical Center, Boston, MA, USA
| | | | - Sunanda V Kane
- Department of Gastroenterology and Hepatology, Mayo Clinic, 200 1ST St SW, Rochester, MN, 55905, USA
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Abdulla M, Mohammed N. A Review on Inflammatory Bowel Diseases: Recent Molecular Pathophysiology Advances. Biologics 2022; 16:129-140. [PMID: 36118798 PMCID: PMC9481278 DOI: 10.2147/btt.s380027] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2022] [Accepted: 08/27/2022] [Indexed: 11/24/2022]
Abstract
Inflammatory bowel diseases are considered immune disorders with a complex genetic architecture involving constantly changing endogenous and exogenous factors. The rapid evolution of genomic technologies and the emergence of newly discovered molecular actors are compelling the research community to reevaluate the knowledge and molecular processes. The human intestinal tract contains intestinal human microbiota consisting of commensal, pathogenic, and symbiotic strains leading to immune responses that can contribute and lead to both systemic and intestinal disorders including IBD. In this review, we attempted to highlight some updates of the new IBD features related to genomics, microbiota, new emerging therapies and some major established IBD risk factors.
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Affiliation(s)
- Maheeba Abdulla
- Internal Medicine Department, Ibn AlNafees Hospital, Arabian Gulf University, Manama, Bahrain
- Correspondence: Maheeba Abdulla, Consultant Gastroenterologist, Internal Medicine Department, Ibn AlNafees Hospital, Arabian Gulf University, Manama, Bahrain, Email
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Nørgård BM, Catalini L, Jølving LR, Larsen MD, Friedman S, Fedder J. The Efficacy of Assisted Reproduction in Women with a Wide Spectrum of Chronic Diseases - A Review. Clin Epidemiol 2021; 13:477-500. [PMID: 34194244 PMCID: PMC8236837 DOI: 10.2147/clep.s310795] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Accepted: 05/07/2021] [Indexed: 01/11/2023] Open
Abstract
Assisted reproductive technology (ART) treatments in women with underlying chronic diseases have become increasingly frequent. The objective of this review is to provide an overview of the literature examining the chance of having a live born child after ART in women with chronic diseases, compared to other women receiving ART. We focused on some of the most prevalent chronic diseases in women during their reproductive years, ie ulcerative colitis, Crohn's disease, rheumatoid arthritis, multiple sclerosis, epilepsy, hyperthyroidism, hypothyroidism, and diabetes mellitus. Secondly, we studied the chance of successful implantation. The literature search was performed in the database Pubmed.gov. including all studies published before October 2020. Title and abstracts of 58 papers were reviewed, 37 papers were excluded and other 8 studies were excluded after full-text evaluation. Only 13 papers were eligible for review. Results indicate that women with ulcerative colitis, Crohn's disease, rheumatoid arthritis, hyperthyroidism, and diabetes mellitus type 2 might have problems with low implantation rate or early embryo development during ART. On the contrary, the few studies on women with hypothyroidism, diabetes mellitus type 1, and epilepsy suggest an equivalent chance of a live birth compared to other women undergoing ART. A possible explanation behind these differences could reside in the disease-specific dysregulation of the innate or adaptive immune system. To our knowledge, this is the first review on ART in women with chronic diseases, and it has disclosed that the evidence in this area is indeed sparse. We encourage others to examine live birth after ART in women with chronic diseases.
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Affiliation(s)
- Bente Mertz Nørgård
- Center for Clinical Epidemiology, Odense University Hospital, Odense, Denmark
- Research Unit of Clinical Epidemiology, Department of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Laura Catalini
- Centre of Andrology and Fertility Clinic, Odense University Hospital, Odense, Denmark
- Research Unit of Gynecology and Obstetrics, Department of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Line Riis Jølving
- Center for Clinical Epidemiology, Odense University Hospital, Odense, Denmark
- Research Unit of Clinical Epidemiology, Department of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Michael Due Larsen
- Center for Clinical Epidemiology, Odense University Hospital, Odense, Denmark
- Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
| | - Sonia Friedman
- Center for Clinical Epidemiology, Odense University Hospital, Odense, Denmark
- Center for Crohn’s and Colitis, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Jens Fedder
- Centre of Andrology and Fertility Clinic, Odense University Hospital, Odense, Denmark
- Research Unit of Gynecology and Obstetrics, Department of Clinical Research, University of Southern Denmark, Odense, Denmark
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Romanowska-Próchnicka K, Felis-Giemza A, Olesińska M, Wojdasiewicz P, Paradowska-Gorycka A, Szukiewicz D. The Role of TNF-α and Anti-TNF-α Agents during Preconception, Pregnancy, and Breastfeeding. Int J Mol Sci 2021; 22:ijms22062922. [PMID: 33805757 PMCID: PMC7998738 DOI: 10.3390/ijms22062922] [Citation(s) in RCA: 71] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Accepted: 03/11/2021] [Indexed: 12/15/2022] Open
Abstract
Tumor necrosis factor-alpha (TNF-α) is a multifunctional Th1 cytokine and one of the most important inflammatory cytokines. In pregnancy, TNF-α influences hormone synthesis, placental architecture, and embryonic development. It was also shown that increased levels of TNF-α are associated with pregnancy loss and preeclampsia. Increased TNF-α levels in complicated pregnancy draw attention to trophoblast biology, especially migratory activity, syncytialisation, and endocrine function. Additionally, elevated TNF-α levels may affect the maternal-fetal relationship by altering the secretory profile of placental immunomodulatory factors, which in turn affects maternal immune cells. There is growing evidence that metabolic/pro-inflammatory cytokines can program early placental functions and growth in the first trimester of pregnancy. Furthermore, early pregnancy placenta has a direct impact on fetal development and maternal immune system diseases that release inflammatory (e.g., TNF-α) and immunomodulatory factors, such as chronic inflammatory rheumatic, gastroenterological, or dermatological diseases, and may result in an abnormal release of cytokines and chemokines in syncytiotrophoblasts. Pregnancy poses a challenge in the treatment of chronic disease in patients who plan to have children. The activity of the disease, the impact of pregnancy on the course of the disease, and the safety of pharmacotherapy, including anti-rheumatic agents, in pregnancy should be considered.
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Affiliation(s)
- Katarzyna Romanowska-Próchnicka
- Department of Biophysics and Human Physiology, Faculty of Health Sciences, Warsaw Medical University, 02-091 Warsaw, Poland; (K.R.-P.); (P.W.); (D.S.)
- Department of Connective Tissue Diseases, National Institute of Geriatrics, Rheumatology and Rehabilitation, 02-637 Warsaw, Poland;
| | - Anna Felis-Giemza
- Department of Connective Tissue Diseases, National Institute of Geriatrics, Rheumatology and Rehabilitation, 02-637 Warsaw, Poland;
- Correspondence:
| | - Marzena Olesińska
- Department of Connective Tissue Diseases, National Institute of Geriatrics, Rheumatology and Rehabilitation, 02-637 Warsaw, Poland;
| | - Piotr Wojdasiewicz
- Department of Biophysics and Human Physiology, Faculty of Health Sciences, Warsaw Medical University, 02-091 Warsaw, Poland; (K.R.-P.); (P.W.); (D.S.)
| | - Agnieszka Paradowska-Gorycka
- Department of Molecular Biology, National Institute of Geriatrics, Rheumatology and Rehabilitation, 02-637 Warsaw, Poland;
| | - Dariusz Szukiewicz
- Department of Biophysics and Human Physiology, Faculty of Health Sciences, Warsaw Medical University, 02-091 Warsaw, Poland; (K.R.-P.); (P.W.); (D.S.)
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Cao RH, Grimm MC. Pregnancy and medications in inflammatory bowel disease. Obstet Med 2021; 14:4-11. [PMID: 33995565 PMCID: PMC8107959 DOI: 10.1177/1753495x20919214] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2019] [Revised: 01/20/2020] [Accepted: 02/21/2020] [Indexed: 12/27/2022] Open
Abstract
Inflammatory bowel disease (IBD) affects patients at a significant time in their lives, often coinciding with family planning or pregnancy. While advances in IBD therapies have afforded women greater opportunities for successful conception and pregnancy outcomes, there still remains considerable maternal fear surrounding continuation of treatment in pregnancy. With the exception of methotrexate, most IBD drugs are safe and well tolerated during pregnancy and are not associated with significant risk of adverse fetal or pregnancy outcomes. Furthermore, the current evidence overwhelmingly suggests that good control of disease activity and clinical remission at time of conception are the greatest prognostic factors for an uncomplicated pregnancy and maintenance of quiescent disease. Management of pregnant women with IBD should involve discussions with the mother and family about fears or concerns surrounding the impact of IBD on pregnancy. Mothers should be supported and counselled carefully on the safety and importance of adherence to therapy in maintaining remission. Optimal management of these women requires an inter-disciplinary team effort, involving the general practitioner, in close consultation with both gastroenterologists and obstetricians.
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Affiliation(s)
- Rena H Cao
- St George and Sutherland Clinical School,
University of New South Wales, Sydney, Australia
| | - Michael C Grimm
- St George and Sutherland Clinical School,
University of New South Wales, Sydney, Australia
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12
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Cooley LF, Wren J, Keeter MK, Lam I, Bennett N, Brannigan RE. Anti-TNF agents and potential effects on male fertility: are men being counseled? BMC Urol 2020; 20:111. [PMID: 32718310 PMCID: PMC7385975 DOI: 10.1186/s12894-020-00658-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2019] [Accepted: 06/22/2020] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Adult men with autoimmune conditions are commonly prescribed anti-tumor necrosis factor (anti-TNF) agents; however, there is a paucity of quality evidence as to their effect on male fertility (e.g. semen parameters and sperm quality). Our objective was to determine if men with autoimmune conditions are being counseled regarding the unknown reproductive effects of anti-TNF agents prior to initiation of therapy. METHODS A retrospective analysis of 1010 male patients age 18-45 who were prescribed an anti-TNF agent were assessed for (1) receipt of counseling regarding potential reproductive effects; (2) screening for anatomic or laboratory abnormalities associated with infertility; (3) election for sperm cryopreservation. RESULTS Only 10.3% of men received counseling, and this was not associated with age (p = 0.77). Those who received counseling were significantly more likely to have a genitourinary exam performed, be assessed for presence of a varicocele, be asked about or endorse low libido or erectile dysfunction, have a testosterone, LH, FSH, or prolactin level checked, and have a semen analysis performed (all, p < 0.0001). Rates of sperm cryopreservation were low, but statistically higher in men who received counseling (5.77% (+) counseling, 1.10% (-) counseling) (p = 0.002). CONCLUSIONS The limited current literature lacks a consensus regarding the short- and long-term male reproductive effects of anti-TNF therapy. Despite this lack of clarity, rates of pre-initiation counseling were low. Rates of sperm cryopreservation, while improved in the counseled group remained low, suggesting prescribing physicians may be unaware of this option for patients.
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Affiliation(s)
- Lauren Folgosa Cooley
- Department of Urology, Northwestern University Feinberg School of Medicine, 676 N. St. Clair St. Arkes 23-015, Chicago, IL, 60611, USA
| | - James Wren
- Department of Urology, Northwestern University Feinberg School of Medicine, 676 N. St. Clair St. Arkes 23-015, Chicago, IL, 60611, USA
| | - Mary Kate Keeter
- Department of Urology, Northwestern University Feinberg School of Medicine, 676 N. St. Clair St. Arkes 23-015, Chicago, IL, 60611, USA
| | - Isaac Lam
- Department of Urology, Northwestern University Feinberg School of Medicine, 676 N. St. Clair St. Arkes 23-015, Chicago, IL, 60611, USA
| | - Nelson Bennett
- Department of Urology, Northwestern University Feinberg School of Medicine, 676 N. St. Clair St. Arkes 23-015, Chicago, IL, 60611, USA
| | - Robert E Brannigan
- Department of Urology, Northwestern University Feinberg School of Medicine, 676 N. St. Clair St. Arkes 23-015, Chicago, IL, 60611, USA.
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13
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Sood A, Ahuja V, Midha V, Sinha SK, Pai CG, Kedia S, Mehta V, Bopanna S, Abraham P, Banerjee R, Bhatia S, Chakravartty K, Dadhich S, Desai D, Dwivedi M, Goswami B, Kaur K, Khosla R, Kumar A, Mahajan R, Misra SP, Peddi K, Singh SP, Singh A. Colitis and Crohn's Foundation (India) consensus statements on use of 5-aminosalicylic acid in inflammatory bowel disease. Intest Res 2020; 18:355-378. [PMID: 32646198 PMCID: PMC7609395 DOI: 10.5217/ir.2019.09176] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2019] [Accepted: 04/04/2020] [Indexed: 12/16/2022] Open
Abstract
Despite several recent advances in therapy in inflammatory bowel disease (IBD), 5-aminosalicylic acid (5-ASA) therapy has retained its place especially in ulcerative colitis. This consensus on 5-ASA is obtained through a modified Delphi process, and includes guiding statements and recommendations based on literature evidence (randomized trials, and observational studies), clinical practice, and expert opinion on use of 5-ASA in IBD by Indian gastroenterologists. The aim is to aid practitioners in selecting appropriate treatment strategies and facilitate optimal use of 5-ASA in patients with IBD.
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Affiliation(s)
- Ajit Sood
- Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, India
| | - Vineet Ahuja
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Vandana Midha
- Department of Internal Medicine, Dayanand Medical College and Hospital, Ludhiana, India
| | - Saroj Kant Sinha
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - C Ganesh Pai
- Department of Gastroenterology, Kasturba Medical College, Manipal, India
| | - Saurabh Kedia
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Varun Mehta
- Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, India
| | | | - Philip Abraham
- P. D. Hinduja Hospital and Medical Research Centre, Mumbai, India
| | - Rupa Banerjee
- Asian Institute of Gastroenterology, Hyderabad, India
| | - Shobna Bhatia
- Department of Gastroenterology, King Edward Memorial Hospital, Mumbai, India
| | | | - Sunil Dadhich
- Department of Gastroenterology, Dr. Sampurnanand Medical College, Jodhpur, India
| | - Devendra Desai
- P. D. Hinduja Hospital and Medical Research Centre, Mumbai, India
| | - Manisha Dwivedi
- Department of Gastroenterology, Moti Lal Nehru Medical College, Allahabad, India
| | - Bhabhadev Goswami
- Department of Gastroenterology, Gauhati Medical College, Guwahati, India
| | - Kirandeep Kaur
- Department of Pharmacology, Dayanand Medical College and Hospital, Ludhiana, India
| | - Rajeev Khosla
- Max Super Speciality Hospital, Saket, New Delhi, India
| | - Ajay Kumar
- BLK Super Speciality Hospital, New Delhi, India
| | - Ramit Mahajan
- Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, India
| | - S P Misra
- Department of Gastroenterology, Moti Lal Nehru Medical College, Allahabad, India
| | - Kiran Peddi
- Citizens Centre for Digestive Disorders, Hyderabad, India
| | - Shivaram Prasad Singh
- Department of Gastroenterology, Sriram Chandra Bhanj Medical College and Hospital, Cuttack, India
| | - Arshdeep Singh
- Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, India
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14
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Geldhof A, Slater J, Clark M, Chandran U, Coppola D. Exposure to Infliximab During Pregnancy: Post-Marketing Experience. Drug Saf 2020; 43:147-161. [PMID: 31677004 PMCID: PMC7007430 DOI: 10.1007/s40264-019-00881-8] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Background Women of childbearing potential are often treated with monoclonal antibodies to control chronic and debilitating inflammatory diseases. Remicade® (innovator infliximab [IFX]) may cross the placenta after the first trimester of pregnancy. Hence, evidence is needed to optimize treatment while carefully weighing benefits and risks to the mother and child. Here, we report on birth and infant outcomes (up to 2 years) following gestational exposure to IFX based on a summary of cumulative pregnancy reports in women exposed to IFX during pregnancy from the Janssen global safety database. Methods Prospective and medically confirmed safety data on IFX-exposed pregnancies from Janssen’s global safety surveillance database since authorization in 1998 are summarized. Descriptive statistics were used to summarize pregnancy and infant outcomes overall, by disease and timing of exposure. Results As of 23 August 2018, 1850 maternally IFX-exposed pregnancies with known outcomes were identified from the safety database. Of the 1850 pregnancies (mean age 29.7 years), 1526 (82.5%) resulted in live births. When reported, most women had Crohn’s disease (67.7%) or ulcerative colitis (18.4%), and 82.8% of live births were exposed to IFX in the first trimester. Spontaneous abortion/intrauterine death/ectopic pregnancy/molar pregnancy (12.1%), preterm births (9.2%), low birth weight infants (3.6%), congenital anomalies (2.0%), and infant infections (1.2%) were documented. The type of congenital anomalies and frequency of serious infant infections observed were consistent with the general population. Frequencies of congenital anomalies and other adverse outcomes were similar in women exposed to IFX in the first trimester and those exposed in the third trimester. More preterm births (13–18.8%) and infant complications (8.7–12.5%) were reported with concomitant immunosuppressant use. Conclusions The observed prevalence of adverse pregnancy and infant outcomes including congenital anomalies following exposure to IFX did not exceed estimates reported for the general population and no unexpected patterns were observed.
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Affiliation(s)
- Anja Geldhof
- Janssen Biologics B.V., Medical Affairs, Einsteinweg 101, 2333, Leiden, CB, The Netherlands.
| | | | - Michael Clark
- Janssen Research and Development, Spring House, PA, USA
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15
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Foulon A, Chevreau J, Yzet C, Gondry J, Fumery M. [IBD and pregnancy: From conception to birth]. ACTA ACUST UNITED AC 2020; 48:514-519. [PMID: 32145453 DOI: 10.1016/j.gofs.2020.02.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2019] [Indexed: 10/24/2022]
Abstract
Inflammatory Bowel Diseases (IBD) are chronic conditions affecting young people in their reproductive age. Patient misinformation can be responsible for a self-imposed infertility as well as a suboptimal observance during pregnancy. The aim of this work was to review the influence of IBD and pregnancy on one another at each gestational stage and according to current literature. IBD activity is a major influential factor. In case of a well-controlled IBD, fertility won't be affected and pregnancy will take place without increase risk of complications. With the exception of thalidomide and methotrexate, most of treatments used in IBD are compatible with pregnancy and breastfeeding. Each flare should be optimally managed. Vaginal delivery is a safe option except for patients with active anoperineal lesions. Cesarean section should be systematically discuss in patient with ileal pouch-anal anastomosis.
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Affiliation(s)
- A Foulon
- Centre de gynécologie-obstétrique, CHU Amiens-Picardie, 1, rue du Professeur-Christian-Cabrol, 80054 Amiens, France.
| | - J Chevreau
- Centre de gynécologie-obstétrique, CHU Amiens-Picardie, 1, rue du Professeur-Christian-Cabrol, 80054 Amiens, France
| | - C Yzet
- Service de gastro-entérologie, CHU Amiens-Picardie, 1, rue du Professeur-Christian-Cabrol, 80054 Amiens, France; Université Picardie-Jules-Vernes, UFR de médecine, 3, rue des Louvels, 80000 Amiens, France
| | - J Gondry
- Centre de gynécologie-obstétrique, CHU Amiens-Picardie, 1, rue du Professeur-Christian-Cabrol, 80054 Amiens, France; Université Picardie-Jules-Vernes, UFR de médecine, 3, rue des Louvels, 80000 Amiens, France
| | - M Fumery
- Service de gastro-entérologie, CHU Amiens-Picardie, 1, rue du Professeur-Christian-Cabrol, 80054 Amiens, France; Université Picardie-Jules-Vernes, UFR de médecine, 3, rue des Louvels, 80000 Amiens, France
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16
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Moreno CC, Mittal PK, Miller FH. Nonfetal Imaging During Pregnancy: Acute Abdomen/Pelvis. Radiol Clin North Am 2019; 58:363-380. [PMID: 32044012 DOI: 10.1016/j.rcl.2019.10.005] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Abdominal pain is a common occurrence in pregnant women and may have a variety of causes, including those that are specific to pregnancy (eg, round ligament pain in the first trimester) and the wide range of causes of abdominal pain that affect men and women who are not pregnant (eg, appendicitis, acute cholecystitis). Noncontrast magnetic resonance (MR) imaging is increasingly performed to evaluate pregnant women with abdominal pain, either as the first-line test or as a second test following ultrasonography. The imaging appearance of causes of abdominal pain in pregnant women are reviewed with an emphasis on noncontrast MR imaging.
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Affiliation(s)
- Courtney C Moreno
- Department of Radiology and Imaging Sciences, Emory University School of Medicine, 1364-A Clifton Road Northeast Suite AT-627, Atlanta, GA 30327, USA.
| | - Pardeep K Mittal
- Department of Radiology, Medical College of Georgia, 1120 15th Street, BA-1411, Augusta, GA 30912, USA
| | - Frank H Miller
- Body Imaging Section and Fellowship, MRI, Department of Radiology, Northwestern University Feinberg School of Medicine, 676 North Saint Clair, Suite 800, Chicago, IL 60611, USA
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17
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Leenhardt R, Rivière P, Papazian P, Nion-Larmurier I, Girard G, Laharie D, Marteau P. Sexual health and fertility for individuals with inflammatory bowel disease. World J Gastroenterol 2019; 25:5423-5433. [PMID: 31576090 PMCID: PMC6767981 DOI: 10.3748/wjg.v25.i36.5423] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2019] [Revised: 08/05/2019] [Accepted: 08/19/2019] [Indexed: 02/06/2023] Open
Abstract
The impact of a chronic disease such as inflammatory bowel disease (IBD) on sexual functioning and body image can significantly impair the quality of life of patients. This review considers the sexual and fertility aspects of IBD patients and their daily management. Modern IBD healthcare management should include appropriate communication on sexuality and consider psychological, physiological, and biological issues. Patients with IBD have less children than the general population, and voluntary childlessness is frequent. The most influential factors reported by IBD patients who experience fertility alteration are psychological and surgery-related problems. Pregnancy is a major concern for patients, and any pregnancy for IBD patients should be closely followed-up to keep the chronic disease in a quiescent state. Preconceptional consultation is of great help.
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Affiliation(s)
- Romain Leenhardt
- Sorbonne Université, Hépatologie, Gastroentérologie et Saint Antoine IBD NeTwork, APHP, Hôpital St Antoine, Paris 75012, Ile-de-France, France
| | - Pauline Rivière
- CHU de Bordeaux, Hôpital Haut-Lévêque, Service d'Hépato-gastroentérologie, CMC Magellan, Bordeaux 33604, Pessac, France
| | - Patrick Papazian
- Hôpital Bichat, Service des maladies infectieuses et tropicales, APHP, Paris 75018, France
| | - Isabelle Nion-Larmurier
- Sorbonne Université, Hépatologie, Gastroentérologie et Saint Antoine IBD NeTwork, APHP, Hôpital St Antoine, Paris 75012, Ile-de-France, France
| | - Guillaume Girard
- Service de gynécologie obstétrique, Hôpital Armand Trousseau, Paris 75012, Ile-de-France, France
| | - David Laharie
- CHU de Bordeaux, Hôpital Haut-Lévêque, Service d'Hépato-gastroentérologie, CMC Magellan, Bordeaux 33604, Pessac, France
| | - Philippe Marteau
- Sorbonne Université, Hépatologie, Gastroentérologie et Saint Antoine IBD NeTwork, APHP, Hôpital St Antoine, Paris 75012, Ile-de-France, France
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18
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Lee S, Crowe M, Seow CH, Kotze PG, Kaplan GG, Metcalfe A, Ricciuto A, Benchimol EI, Kuenzig ME, Cochrane IBD Group. The impact of surgical therapies for inflammatory bowel disease on female fertility. Cochrane Database Syst Rev 2019; 7:CD012711. [PMID: 31334846 PMCID: PMC6647933 DOI: 10.1002/14651858.cd012711.pub2] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND Women with inflammatory bowel disease (IBD) may require surgery, which may result in higher risk of infertility. Restorative proctocolectomy with ileal anal pouch anastomosis (IPAA) may increase infertility, but the degree to which IPAA affects infertility remains unclear, and the impact of other surgical interventions on infertility is unknown. OBJECTIVES Primary objective• To determine the effects of surgical interventions for IBD on female infertility.Secondary objectives• To evaluate the impact of surgical interventions on the need for assisted reproductive technology (ART), time to pregnancy, miscarriage, stillbirth, prematurity, mode of delivery (spontaneous vaginal, instrumental vaginal, or Caesarean section), infant requirement for resuscitation and neonatal intensive care, low and very low birth weight, small for gestational age, antenatal and postpartum hemorrhage, retained placenta, postpartum depression, gestational diabetes, and gestational hypertension/preeclampsia. SEARCH METHODS We searched MEDLINE, Embase, CENTRAL, and the Cochrane IBD Group Specialized Register from inception to September 27, 2018, to identify relevant studies. We also searched references of relevant articles, conference abstracts, grey literature, and trials registers. SELECTION CRITERIA We included observational studies that compared women of reproductive age (≥ 12 years of age) who underwent surgery to women with IBD who had a different type of surgery or no surgery (i.e. treated medically). We also included studies comparing women before and after surgery. Any type of IBD-related surgery was permitted. Infertility was defined as an inability to become pregnant following 12 months of unprotected intercourse. Infertility at 6, 18, and 24 months was included as a secondary outcome. We excluded studies that included women without IBD and those comparing women with IBD to women without IBD.. DATA COLLECTION AND ANALYSIS Two review authors independently screened studies and extracted data. We used the Newcastle-Ottawa Scale to assess bias and GRADE to assess the overall certainty of evidence. We calculated the pooled risk ratio (RR) and 95% confidence interval (CI) using random-effects models. When individual studies reported odds ratios (ORs) and did not provide raw numbers, we pooled ORs instead. MAIN RESULTS We identified 16 observational studies for inclusion. Ten studies were included in meta-analyses, of which nine compared women with and without a previous IBD-related surgery and the other compared women with open and laparoscopic IPAA. Of the ten studies included in meta-analyses, four evaluated infertility, one evaluated ART, and seven reported on pregnancy-related outcomes. Seven studies in which women were compared before and after colectomy and/or IPAA were summarized qualitatively, of which five included a comparison of infertility, three included the use of ART, and three included other pregnancy-related outcomes. One study included a comparison of women with and without IPAA, as well as before and after IPAA, and was therefore included in both the meta-analysis and the qualitative summary. All studies were at high risk of bias for at least two domains.We are very uncertain of the effect of IBD surgery on infertility at 12 months (RR 5.45, 95% CI 0.41 to 72.57; 114 participants; 2 studies) and at 24 months (RR 3.59, 95% CI 1.32 to 9.73; 190 participants; 1 study). Infertility was lower in women who received laparoscopic surgery compared to open restorative proctocolectomy at 12 months (RR 0.70, 95% CI 0.38 to 1.27; 37 participants; 1 study).We are very uncertain of the effect of IBD surgery on pregnancy-related outcomes, including miscarriage (OR 2.03, 95% CI 1.14 to 3.60; 776 pregnancies; 5 studies), use of ART (RR 25.09, 95% CI 1.56 to 403.76; 106 participants; 1 study), delivery via Caesarean section (RR 2.23, 95% CI 1.00 to 4.95; 20 pregnancies; 1 study), stillbirth (RR 1.96, 95% CI 0.42 to 9.18; 246 pregnancies; 3 studies), preterm birth (RR 1.91, 95% CI 0.67 to 5.48; 194 pregnancies; 3 studies), low birth weight (RR 0.61, 95% CI 0.08 to 4.83), and small for gestational age (RR 2.54, 95% CI 0.80 to 8.01; 65 pregnancies; 1 study).Studies comparing infertility before and after IBD-related surgery reported numerically higher rates of infertility at six months (before: 1/5, 20.0%; after: 9/15, 60.0%; 1 study), at 12 months (before: 68/327, 20.8%; after: 239/377, 63.4%; 5 studies), and at 24 months (before: 14/89, 15.7%; after: 115/164, 70.1%; 2 studies); use of ART (before: 5.3% to 42.2%; after: 30.3% to 34.3%; proportions varied across studies due to differences in which women were identified as at risk of using ART); and delivery via Caesarean section (before: 8/73, 11.0%; after: 36/75, 48.0%; 2 studies). In addition, women had a longer time to conception after surgery (two to five months; 2 studies) than before surgery (5 to 16 months; 2 studies). The proportions of women experiencing miscarriage (before: 19/123, 15.4%; after: 21/134, 15.7%; 3 studies) and stillbirth (before: 2/38, 5.3%; after: 3/80: 3.8%; 2 studies) were similar before and after surgery. Fewer women experienced gestational diabetes after surgery (before: 3/37, 8.1%; after: 0/37; 1 study), and the risk of preeclampsia was similar before and after surgery (before: 2/37, 5.4%; after: 0/37; 1 study). We are very uncertain of the effects of IBD-related surgery on these outcomes due to poor quality evidence, including confounding bias due to increased age of women after surgery.We rated evidence for all outcomes and comparisons as very low quality due to the observational nature of the data, inclusion of small studies with imprecise estimates, and high risk of bias among included studies. AUTHORS' CONCLUSIONS The effect of surgical therapy for IBD on female infertility is uncertain. It is also uncertain if there are any differences in infertility among those undergoing open versus laparoscopic procedures. Previous surgery was associated with higher risk of miscarriage, use of ART, Caesarean section delivery, and giving birth to a low birth weight infant, but was not associated with risk of stillbirth, preterm delivery, or delivery of a small for gestational age infant. These findings are based on very low-quality evidence. As a result, definitive conclusions cannot be made, and future well-designed studies are needed to fully understand the impact of surgery on infertility and pregnancy outcomes.
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Affiliation(s)
- Sangmin Lee
- University of CalgaryCommunity Health SciencesCalgaryABCanada
| | - Megan Crowe
- University of OttawaSchool of Epidemiology and Public HealthOttawaONCanada
| | - Cynthia H Seow
- University of CalgaryDepartment of MedicineTRW Building Rm 6D183280 Hospital Drive NWCalgaryABCanadaT2N 4Z6
| | - Paulo G Kotze
- Catholic University of Paraná (PUCPR)IBD Outpatients Clinic, Colorectal Surgery UnitCuritibaBrazil
| | - Gilaad G Kaplan
- University of CalgaryDepartment of MedicineTRW Building Rm 6D183280 Hospital Drive NWCalgaryABCanadaT2N 4Z6
| | - Amy Metcalfe
- University of CalgaryDepartment of Obstetrics & GynecologyCalgaryAlbertaCanada
| | - Amanda Ricciuto
- The Hospital for Sick ChildrenDivision of Gastroenterology, Hepatology & NutritionTorontoONCanada
| | - Eric I Benchimol
- The Children's Hospital of Eastern OntarioDivision of Gastroenterology Hepatology & Nutrition401 Smyth RoadOttawaONCanadaK1H 8L1
- University of OttawaDepartment of PediatricsOttawaONCanada
| | - M Ellen Kuenzig
- The Children's Hospital of Eastern OntarioDivision of Gastroenterology Hepatology & Nutrition401 Smyth RoadOttawaONCanadaK1H 8L1
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19
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Avellar MCW, Ribeiro CM, Dias-da-Silva MR, Silva EJR. In search of new paradigms for epididymal health and disease: innate immunity, inflammatory mediators, and steroid hormones. Andrology 2019; 7:690-702. [PMID: 31207127 DOI: 10.1111/andr.12654] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2018] [Revised: 04/22/2019] [Accepted: 04/29/2019] [Indexed: 02/07/2023]
Abstract
The primary job of the epididymis is to mature and protect the luminally transiting spermatozoa. Mounting evidence is showing that innate immune components [including Toll-like receptors (TLRs) and antimicrobial proteins, among which are β-defensins] and inflammatory mediators, under the primary influence of androgens, participate in the cellular and molecular processes that define this tissue. Here, we present an overview of the contributions of these signaling pathway components during epididymal homeostasis and discuss the hypotheses as to their involvement in epididymitis, the most common urological inflammatory condition in men, frequently impairing their fertility. Drawing primarily from rodent models, we also focus on how the distribution and functional expression of innate immune components are differentially regulated in the prenatal developing epididymis, providing new insights into the disruption of these signaling pathways throughout the lifespan. Male infertility is caused by a variety of conditions, such as congenital malformations, genetic and endocrine disorders, exposure to environmental toxicants, and inflammatory/infectious conditions. More than one-third of infertile men with an idiopathic condition cannot currently be adequately diagnosed. Thinking about the innate immunity and inflammation context of the epididymis may provide new insights and directions as to how these systems contribute to male fertility, as well as also uncover urological and andrological outcomes that may aid clinicians in diagnosing and preventing epididymal pathologies.
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Affiliation(s)
- M C W Avellar
- Department of Pharmacology, Universidade Federal de São Paulo - Escola Paulista de Medicina, São Paulo, SP, Brazil
| | - C M Ribeiro
- Department of Pharmacology, Universidade Federal de São Paulo - Escola Paulista de Medicina, São Paulo, SP, Brazil
| | - M R Dias-da-Silva
- Department of Medicine, Universidade Federal de São Paulo - Escola Paulista de Medicina, São Paulo, SP, Brazil
| | - E J R Silva
- Department of Pharmacology, Institute of Biosciences of Botucatu, Universidade Estadual Paulista 'Júlio de Mesquita Filho', Botucatu, SP, Brazil
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20
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Safety of anti-rheumatic drugs in men trying to conceive: A systematic review and analysis of published evidence. Semin Arthritis Rheum 2019; 48:911-920. [DOI: 10.1016/j.semarthrit.2018.07.011] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2018] [Revised: 05/18/2018] [Accepted: 07/23/2018] [Indexed: 12/31/2022]
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21
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Park YE, Kim TO. Sexual Dysfunction and Fertility Problems in Men with Inflammatory Bowel Disease. World J Mens Health 2019; 38:285-297. [PMID: 30929327 PMCID: PMC7308231 DOI: 10.5534/wjmh.190007] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2019] [Revised: 01/29/2019] [Accepted: 02/10/2019] [Indexed: 12/14/2022] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract that is usually diagnosed in young individuals. Crohn's disease and ulcerative colitis are the 2 principal forms of IBD. Patients with IBD demonstrate varying degrees of disease activity and sometimes need to undergo bowel surgery such as proctocolectomy with ileal pouch-anal anastomosis that involves removal of the entire colon and rectum with consequent sexual dysfunction. Several studies have shown that sulfasalazine, affects male fertility. Additionally, many men with IBD are unable to control their smoking, drinking, and eating habits, which can cause worsening of disease activity and fertility. Therefore, infertility and sexual dysfunction are important issues in young patients diagnosed with IBD because they are related to optimal management of the disease and patients' quality of life. Only a few studies have reported sexual dysfunction and infertility in men with IBD. Therefore, this study reviewed the current literature describing male sexual dysfunction scales and evaluated the causes of sexual dysfunction and infertility in men with IBD.
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Affiliation(s)
- Yong Eun Park
- Division of Gastroenterology, Department of Internal Medicine, Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea
| | - Tae Oh Kim
- Division of Gastroenterology, Department of Internal Medicine, Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea.
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22
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Paternal exposure to antirheumatic drugs—What physicians should know: Review of the literature. Semin Arthritis Rheum 2018; 48:343-355. [DOI: 10.1016/j.semarthrit.2018.01.006] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2017] [Revised: 12/19/2017] [Accepted: 01/09/2018] [Indexed: 12/11/2022]
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Gastro-intestinal surgery and fertility. J Visc Surg 2018; 155 Suppl 1:S49-S55. [PMID: 29857942 DOI: 10.1016/j.jviscsurg.2018.04.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
In France, 10 to 15% of couples in the overall population have a fertility problem. Preservation of sexual and reproductive function should be a major concern for all patients capable of procreation who undergo treatment for gastro-intestinal disease. The gastro-intestinal diseases most often responsible for fertility disorders include chronic inflammatory diseases, intestinal cancer and hereditary diseases, such as the Lynch syndrome and familial adenomatous polyposis. Obesity is responsible for a 20% loss of fertility but the effects of bariatric surgery on fertility are controversial. Nonetheless, in the light of progress in surgical techniques and better knowledge of gastro-intestinal disease the negative impact of surgery on fertility warrants attention. Effectively, fertility can be preserved after certain major gastro-intestinal operations such as cytoreductive surgery with intraperitoneal chemotherapy, total coloprotectomy with ileo-anal anastomosis and rectosigmoid resection, as long as the patient's age permits and resection of the reproductive organs is not necessary.
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Ley D, Jones J, Parrish J, Salih S, Caldera F, Tirado E, Leader B, Saha S. Methotrexate Reduces DNA Integrity in Sperm From Men With Inflammatory Bowel Disease. Gastroenterology 2018; 154:2064-2067.e3. [PMID: 29481778 DOI: 10.1053/j.gastro.2018.02.025] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2017] [Revised: 02/01/2018] [Accepted: 02/19/2018] [Indexed: 01/04/2023]
Abstract
There are few data on the effects of methotrexate on reproductive capacity in men with inflammatory bowel diseases (IBDs). We performed a case-control study to determine the effects of methotrexate on sperm quality and genetic integrity. We compared sperm samples from 7 men with IBD who had been exposed to methotrexate for at least 3 months with sperm samples collected from 1912 age-matched men at fertility centers (controls) where sperm parameters would be expected to be worse than those of the general population. Sperm were evaluated by basic semen analysis and advanced sperm integrity testing. In samples from men with IBD, all basic semen analysis parameters were within normal limits. However, these samples had reduced sperm integrity, based on significant increases in levels of DNA fragmentation and damage from oxidative stress compared with controls. Our findings indicate that methotrexate can reduce DNA integrity in sperm and cause damage via oxidative stress.
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Affiliation(s)
- Dana Ley
- University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
| | - Jeffrey Jones
- Department of Obstetrics and Gynecology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin; UW Health Generations Fertility Care, Middleton, Wisconsin
| | - John Parrish
- Department of Animal Sciences, University of Wisconsin-Madison, Madison, Wisconsin
| | - Sana Salih
- Department of Obstetrics and Gynecology, West Virginia University School of Medicine, Morgantown, West Virginia
| | - Freddy Caldera
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
| | - Edna Tirado
- Clinical Research Division, ReproSource, Inc., Woburn, Massachusetts
| | - Benjamin Leader
- Clinical Research Division, ReproSource, Inc., Woburn, Massachusetts
| | - Sumona Saha
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
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Abstract
There has been considerable literature on sexual issues in women with inflammatory bowel disease (IBD), but relatively little attention has been paid to these aspects in men. To review the available literature and to provide the best management of sexual and reproductive issues in male patients with IBD. The scientific literature on sexual and reproductive issues in men with IBD was reviewed. Several factors, including surgical and medication treatments, disease activity, lifestyle, and psychological factors, may play a role in the development of infertility and sexual dysfunction and may negatively impact pregnancy outcomes. Proctocolectomy with ileal pouch-anal anastomosis increases the risk of erectile and ejaculatory dysfunction by up to 26%. A treatment with sildenafil can be effective. Sperm banking should be advised to young men with IBD before surgery. Both sulfasalazine and methotrexate may be responsible for reversible sexual dysfunction and infertility. Furthermore, sulfasalazine should be switched to mesalazine at least 4 months before conception because of a higher risk of congenital malformations in pregnancies fathered by men treated with this drug. Psychotropic drugs, frequently used in IBD, may cause sexual dysfunction up to 80%. Last but not the least, voluntary childlessness occurs frequently, mainly because of concerns about medication safety in pregnancy and fear of transmitting disease. Accurate counseling, and where necessary, psychological support can decrease any misperceptions and fears. Close collaboration between the gastroenterologist and the patient is recommended for the best management of these relevant, neglected aspects in men with IBD.
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Ommati MM, Heidari R, Jamshidzadeh A, Zamiri MJ, Sun Z, Sabouri S, Wang J, Ahmadi F, Javanmard N, Seifi K, Mousapour S, Yeganeh BS. Dual effects of sulfasalazine on rat sperm characteristics, spermatogenesis, and steroidogenesis in two experimental models. Toxicol Lett 2018; 284:46-55. [DOI: 10.1016/j.toxlet.2017.11.034] [Citation(s) in RCA: 45] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2017] [Revised: 11/21/2017] [Accepted: 11/27/2017] [Indexed: 01/27/2023]
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Bonthala N, Kane S. Updates on Women's Health Issues in Patients with Inflammatory Bowel Disease. CURRENT TREATMENT OPTIONS IN GASTROENTEROLOGY 2018; 16:86-100. [PMID: 29479656 DOI: 10.1007/s11938-018-0172-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
PURPOSE OF REVIEW Inflammatory bowel disease affects approximately 800,000 women in the USA with the peak incidence between ages 15 to 40. Thus for many females, IBD can impact nearly every stage of their life from menarche to pregnancy, menopause, and beyond. This paper will review the most recent updates on the topics of sexual health, cervical cancer screening, menstruation, fertility, contraception, and menopause. RECENT FINDINGS Menarche can be delayed in females especially those who are underweight, malnourished, or with active inflammatory bowel disease. Cyclical GI symptoms during a menstrual cycle are very common in women with IBD and should not be confused with flares. Overall fertility is similar to the general population unless females with IBD have had significant abdominal surgery but reassuringly this infertility appears to be restored with the use of in vitro fertilization. Discussion regarding family planning is imperative in women with IBD with a strong recommendation to consider long-acting highly effective contraceptives such as intrauterine devices or implants. Cervical cancer screening should be tailored in women on immunosuppressive medications and all women under 26 years of age should be advised to receive the human papilloma virus vaccination. As gastroenterologists will have longitudinal relationships with their female IBD patients, they must be knowledgeable about sex-specific issues during each stage of life from puberty to after menopause to optimize their patient's care.
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Affiliation(s)
- Nirupama Bonthala
- Inflammatory Bowel Disease Center, Cedars Sinai Medical Center, Los Angeles, CA, USA
| | - Sunanda Kane
- Department of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN, 55905, USA.
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Birth outcomes after preconception paternal exposure to methotrexate: A nationwide cohort study. Reprod Toxicol 2017; 74:219-223. [DOI: 10.1016/j.reprotox.2017.10.004] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2017] [Revised: 10/03/2017] [Accepted: 10/17/2017] [Indexed: 12/27/2022]
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Martin L, Mullaney S, Peche W, Peterson K, Chan S, Morton R, Wan Y, Zhang C, Presson AP, Emery B, Aston K, Jenkins T, Carrell D, Hotaling J. Population-based Semen Analysis Results and Fertility Among Patients With Inflammatory Bowel Disease: Results From Subfertility Health Assisted Reproduction and the Environment (SHARE) Study. Urology 2017; 107:114-119. [DOI: 10.1016/j.urology.2017.06.029] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2017] [Revised: 06/01/2017] [Accepted: 06/19/2017] [Indexed: 12/18/2022]
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Gutierrez JC, Hwang K. The toxicity of methotrexate in male fertility and paternal teratogenicity. Expert Opin Drug Metab Toxicol 2016; 13:51-58. [PMID: 27590039 DOI: 10.1080/17425255.2017.1230198] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
INTRODUCTION There is a high prevalence of methotrexate (MTX) use in males of reproductive age. The scope of this paper reviews what is known regarding risks to fertility and partners' pregnancy outcomes with regard to MTX use in men. Areas covered: This paper reviews the evidence for current recommendations for MTX use and male fertility and aims to educate professionals regarding MTX use in reproducing males so that patients may be counseled appropriately. A literature search included peer-reviewed sources from PubMed searches and the literature referenced within. Expert opinion: There is a lack of evidence regarding effects of MTX on male fertility. The recommendation to stop MTX three months prior to conception is safe, but is not evidenced by an understanding of the impact of MTX on spermatogenesis or paternal-mediated teratogenicity but rather the timeframe of spermatogenesis. Given the unclear evidence, patients treated with MTX must be counseled on the likelihood of adverse effects of MTX and role of sperm cryopreservation. Future studies are needed to help elucidate the unclear evidence of MTX effects on male fertility and pregnancy outcomes.
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Affiliation(s)
| | - Kathleen Hwang
- b Division of Urology , Rhode Island Hospital , Providence , Rhode Island , USA
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Bar-Gil Shitrit A, Grisaru-Granovsky S, Ben Ya'acov A, Goldin E. Management of Inflammatory Bowel Disease During Pregnancy. Dig Dis Sci 2016; 61:2194-2204. [PMID: 27068171 DOI: 10.1007/s10620-016-4139-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2015] [Accepted: 03/21/2016] [Indexed: 02/08/2023]
Abstract
Inflammatory bowel disease (IBD) usually affects women during their reproductive years and many concerns arise among these young patients. Pre-pregnancy consultation with a multi-disciplinary team is very important. The team should make patients aware of the critical importance of ensuring that conception occurs during a period of disease remission. Conception during an IBD flare-up results in disease activity or even exacerbates disease in two-thirds of women. Exacerbation of the disease is associated with increased frequency of maternal and fetal complications. Drug therapy constitutes a considerable source of patient anxiety but most drugs used for treating IBD are considered safe. Therefore, continuing pharmacological therapy during pregnancy is necessary to maintain disease control. Optimization of pre-conception nutritional status and smoking cessation are also emphasized. The general guideline for most patients, except for active perianal disease patients, is to aim for vaginal delivery in the absence of obstetric contraindications. Consistent, ongoing follow-up, as detailed in this review, should allay the anxieties and fears surrounding continuing immunosuppressive drugs during pregnancy, allowing each patient to attain the optimal conditions for achieving her goal of holding a healthy baby.
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Affiliation(s)
| | - Sorina Grisaru-Granovsky
- Fetal Maternal Medicine, Obstetrics and Gynecology Department, Shaare Zedek Medical Center, Jerusalem, Israel
| | - Ami Ben Ya'acov
- IBD Center, Digestive Diseases Institute, Shaare Zedek Medical Center, Jerusalem, Israel
| | - Eran Goldin
- IBD Center, Digestive Diseases Institute, Shaare Zedek Medical Center, Jerusalem, Israel
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Kane S. IBD: Assisted reproductive technology less successful in ulcerative colitis. Nat Rev Gastroenterol Hepatol 2016; 13:318-320. [PMID: 27147488 DOI: 10.1038/nrgastro.2016.66] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/08/2022]
Affiliation(s)
- Sunanda Kane
- Mayo Clinic College of Medicine Department of Gastroenterology and Hepatology, 200 First Street SW, Rochester, Minnesota 55905, USA
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Abstract
Low-dose methotrexate (MTX) therapy is a well-recognized therapy for many inflammatory conditions such as rheumatoid arthritis, psoriatic arthritis, and psoriasis. More than 20 years ago, the clinical efficacy of MTX was also established for steroid dependent Crohn's disease, but it was never broadly adapted as a treatment modality. More recently, MTX is being increasingly used in the pediatric population with Crohn's disease, both as a single agent as well as a concomitant therapy with anti-tumor necrosis factor-alpha treatment. This review outlines important pharmacological aspects for the therapeutic application of MTX and the current status of MTX as mono- or combination-therapy in both pediatric and adult patients with inflammatory bowel disease including new results of MTX monotherapy in steroid dependent ulcerative colitis.
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Rosenblatt E, Kane S. Sex-Specific Issues in Inflammatory Bowel Disease. Gastroenterol Hepatol (N Y) 2015; 11:592-601. [PMID: 27482181 PMCID: PMC4965619] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/06/2023]
Abstract
Inflammatory bowel disease (IBD) affects approximately 1 in 500 people living in the United States and generally occurs with equal frequency in men and women. However, despite equal sex distribution of the disease, men and women face unique challenges that can significantly impact quality of life. As more is discovered regarding the pathogenesis, clinical manifestations, and treatment of IBD, physiologic and psychological differences between men and women with IBD have become increasingly apparent. It is important to understand these differences, as they have the potential to affect patient care and outcomes. This article will review sex-specific issues in IBD, such as impaired body image and sexuality, increased risk of cervical cancer, altered menstrual cycles, reduced fertility, and low bone mineral density.
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Affiliation(s)
- Elizabeth Rosenblatt
- Dr Rosenblatt is a fellow at the University of Washington in Seattle, Washington. Dr Kane is a professor of medicine in the Department of Gastroenterology and Hepatology at the Mayo Clinic College of Medicine in Rochester, Minnesota
| | - Sunanda Kane
- Dr Rosenblatt is a fellow at the University of Washington in Seattle, Washington. Dr Kane is a professor of medicine in the Department of Gastroenterology and Hepatology at the Mayo Clinic College of Medicine in Rochester, Minnesota
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Optimizing the Care and Health of Women with Inflammatory Bowel Disease. Gastroenterol Res Pract 2015; 2015:435820. [PMID: 26089868 PMCID: PMC4454754 DOI: 10.1155/2015/435820] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2014] [Revised: 04/21/2015] [Accepted: 05/11/2015] [Indexed: 12/24/2022] Open
Abstract
Inflammatory bowel disease (IBD) including both ulcerative colitis and Crohn's disease is increasing worldwide. Although diagnosis is equally found in men and women, the chronicity of IBD poses a unique impact on the milestones of a woman's life. As the gastroenterologist becomes increasingly important in the health maintenance of patients with IBD, this review stresses the unique gender issues in women with IBD related to menstruation, cervical cancer, sexual health, contraception, and menopause that may affect the course of disease, treatment decisions, and quality of life.
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Sands K, Jansen R, Zaslau S, Greenwald D. Review article: the safety of therapeutic drugs in male inflammatory bowel disease patients wishing to conceive. Aliment Pharmacol Ther 2015; 41:821-34. [PMID: 25752753 DOI: 10.1111/apt.13142] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2013] [Revised: 04/27/2013] [Accepted: 02/05/2015] [Indexed: 12/20/2022]
Abstract
BACKGROUND Many therapeutic drugs are used by patients with inflammatory bowel disease, often around the time of conception. The pregnancy outcomes of males and females exposed to these therapeutics needs to be examined and this information is necessary to counsel patients appropriately. AIM To review the literature describing male infertility and inflammatory bowel disease to educate practitioners of the impact of inflammatory bowel disease on male reproduction and the impact of therapeutics on pregnancy outcomes. METHODS We performed a PubMed search using the search terms 'male infertility,' 'Crohn's disease,' 'inflammatory bowel disease,' 'ulcerative colitis,' 'ciprofloxacin AND infertility,' 'metronidazole AND infertility,' 'sulfasalazine AND infertility,' 'azathioprine AND infertility,' 'methotrexate AND infertility,' 'ciclosporin AND infertility,' 'corticosteroids AND infertility,' 'infliximab AND male fertility,' 'infliximab AND infertility,' 'infliximab AND foetus,' 'infliximab AND paternal exposure' and 'infliximab AND sperm.' References from selected papers were reviewed and used if relevant. RESULTS Over half of male patients with IBD have some degree of infertility, compared to 8-17% of the general population. Semen parameters including total count, motility and morphology may be adversely affected by therapeutics. IBD medications in males do not increase foetal risk with the possible exception of azathioprine and mercaptopurine; however, increased foetal risk is seen in other drugs if taken by female patients. CONCLUSIONS It is recognised that male infertility is often impacted with therapeutic drugs used to treat inflammatory bowel disease; however, the effects of the paternal drug exposure at the time of conception and exposure in utero should be considered to counsel patients appropriately.
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Affiliation(s)
- K Sands
- EW Sparrow Hospital Urology Residency, Michigan State University College of Osteopathic Medicine, Lansing, MI, USA
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37
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van der Woude CJ, Ardizzone S, Bengtson MB, Fiorino G, Fraser G, Katsanos K, Kolacek S, Juillerat P, Mulders AGMGJ, Pedersen N, Selinger C, Sebastian S, Sturm A, Zelinkova Z, Magro F. The second European evidenced-based consensus on reproduction and pregnancy in inflammatory bowel disease. J Crohns Colitis 2015; 9:107-124. [PMID: 25602023 DOI: 10.1093/ecco-jcc/jju006] [Citation(s) in RCA: 331] [Impact Index Per Article: 33.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Trying to conceive and being pregnant is an emotional period for those involved. In the majority of patients suffering from inflammatory bowel disease, maintenance therapy is required during pregnancy to control the disease, and disease control might necessitate introduction of new drugs during a vulnerable period. In this updated consensus on the reproduction and pregnancy in inflammatory bowel disease reproductive issues including fertility, the safety of drugs during pregnancy and lactation are discussed.
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38
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Deepak P, Stobaugh DJ. Maternal and foetal adverse events with tumour necrosis factor-alpha inhibitors in inflammatory bowel disease. Aliment Pharmacol Ther 2014; 40:1035-43. [PMID: 25164260 DOI: 10.1111/apt.12936] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2014] [Revised: 01/30/2014] [Accepted: 08/07/2014] [Indexed: 12/17/2022]
Abstract
BACKGROUND Transplacental transfer of tumour necrosis factor-alpha (TNF-α) inhibitors has been shown in mothers receiving therapy for inflammatory bowel disease (IBD). AIM To examine reports of adverse events of these medications in pregnancy. METHODS Individual Safety Reports of adverse events (Jan 2003-June 2012) were accessed from the Food and Drug Administration Adverse Event Reporting System. The study data set was constructed by searching for cases with an indication for medication usage of IBD. The data set was then queried for key terms indicating pregnancy, followed by elimination of cases with potentially teratogenic exposures (FDA category X concomitant medications) as well exposures to study medications through partner or if the medications were discontinued prior to pregnancy. Logistic regression analysis was performed to detect signals for maternal/foetal adverse events with TNF-α inhibitors and/or thiopurines (compared to aminosalicylates). RESULTS A total of 1097 individual Safety Reports in pregnant IBD patients were identified with the majority reported among patients receiving TNF-α inhibitor monotherapy (783 cases, 71.4%). Thiopurine monotherapy (OR 2.55, CI 0.95-6.88) and in combination with TNF-α inhibitors (OR 0.97, CI 0.49-1.93) were not associated with increased odds of maternal/foetal adverse events. Decreased odds for maternal/foetal adverse events were seen with TNF-α inhibitor monotherapy (overall) and specifically with certolizumab monotherapy (OR 0.11, CI 0.05-0.23). CONCLUSIONS In this analysis of adverse events from the Food and Drug Administration Adverse Event Reporting System, use of thiopurine monotherapy or in combination with TNF-α inhibitors was not associated with an increase in maternal/foetal adverse events. Certolizumab monotherapy was associated with a decrease in maternal/foetal adverse events.
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Affiliation(s)
- P Deepak
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
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40
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Abstract
Biologic therapies, including anti-tumor necrosis factor antibody therapy and anti-integrin antibodies, are currently approved for the treatment of and are increasingly being used in patients with moderate to severe inflammatory bowel disease, including Crohn disease and ulcerative colitis. Because patients who require these medications are often in their child-bearing years, knowledge of the safety of these medications before and after pregnancy is imperative. This article summarizes the available data regarding the use of biologic therapy during and after pregnancy, highlighting such issues as safety for mother and newborn, length of medication use during pregnancy, and breastfeeding after pregnancy while on biologic therapy.
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Affiliation(s)
- Sara Horst
- Vanderbilt University Medical Center, 1211 21st Avenue, South 220 Medical Arts Building, Nashville, TN 37232, USA
| | - Sunanda Kane
- Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA.
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41
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Stone RH, Hong J, Jeong H. Pharmacokinetics of monoclonal antibodies used for inflammatory bowel diseases in pregnant women. ACTA ACUST UNITED AC 2014; 4. [PMID: 26539323 DOI: 10.4172/2161-0495.1000209] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
Inflammatory bowel disease (IBD) is a condition of chronic immune response and inflammation of the gastrointestinal tract. Most women with IBD are affected during their reproductive years, and untreated IBD can have detrimental maternal and fetal outcomes. In recent years, many biological therapies including anti-TNF agents (infliximab, adalimumab, and certolizumab) have been developed for the treatment of IBD. An increasing number of IBD patients are treated with these agents during pregnancy. Sporadic reports suggest an absence of negative pregnancy outcomes related to use of anti-TNF agents in women with IBD. However, it is unclear if the physiological changes occurring in pregnancy alter mAb dose requirements for optimal maternal disease management and minimal fetal exposure to therapeutic antibodies. Based on current understanding of the pharmacokinetic profiles for anti-TNF agents in nonpregnant subjects, it appears very likely that physiological changes accompanying pregnancy can alter pharmacokinetics of anti-TNF agents. This review focuses on how such physiological changes may impact disposition of anti-TNF agents during pregnancy. Further improvement in pregnancy outcomes may be achieved in women with IBD by better understanding of pregnancy-mediated changes in the pharmacokinetics of anti-TNF agents.
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Affiliation(s)
- Rebecca H Stone
- Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA
| | - James Hong
- Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA
| | - Hyunyoung Jeong
- Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA ; Department of Biopharmaceutical Sciences, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA
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Seirafi M, de Vroey B, Amiot A, Seksik P, Roblin X, Allez M, Peyrin-Biroulet L, Marteau P, Cadiot G, Laharie D, Boureille A, De Vos M, Savoye G, Rahier JF, Carbonnel F, Bonaz B, Colombel JF, Bouhnik Y. Factors associated with pregnancy outcome in anti-TNF treated women with inflammatory bowel disease. Aliment Pharmacol Ther 2014; 40:363-73. [PMID: 24980270 DOI: 10.1111/apt.12833] [Citation(s) in RCA: 73] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2013] [Revised: 12/11/2013] [Accepted: 05/21/2014] [Indexed: 12/20/2022]
Abstract
BACKGROUND The safety of anti-tumour necrosis factor (TNF) agents during pregnancy is a major concern for child-bearing women and physicians. AIM To assess the impact of anti-TNF therapy on adverse pregnancy and foetal outcomes in women with inflammatory bowel disease (IBD). METHODS Pregnancies occurring during anti-TNF treatment or less than 3 months after its cessation in IBD patients followed in GETAID centres were recorded from January 2009 to December 2010. Ninety-nine pregnancies in women without anti-TNF treatment were identified from the CESAME registry. We compared pregnancy and neonatal outcomes by a case-control study. RESULTS In the 124 IBD patients followed, 133 pregnancies were reported. At the conception time, 23% of patients had active disease. Eighty-eight per cent (n = 117) of the 133 pregnancies followed until delivery resulted in 118 liveborns (one twin pregnancy). Complications were observed in 47 (35%) women and 24 (20%) newborns. In multivariate analysis, factors associated with pregnancy complications were: current smoking (P = 0.004), a B2 (stenotic) phenotype in CD women (P = 0.004), occurrence of a flare during pregnancy (P = 0.006) and a past history of complicated pregnancy (P = 0.007). Current smoking was the only factor associated with severe (i.e. potentially lethal) pregnancy complications (P = 0.02). Having IBD for more than 10 years prior to conception was associated with newborn complications (P = 0.007). No difference was found with the control group for any of the pregnancy and neonatal outcomes. CONCLUSION In our series, the safety profile of anti-TNF therapy during pregnancy and the neonatal period appears similar to control group of IBD women not treated with anti-TNF therapy.
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Affiliation(s)
- M Seirafi
- Beaujon University Hospital Paris VII University, Clichy, France; Geneva University Hospital, Geneva, Switzerland
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Palomba S, Sereni G, Falbo A, Beltrami M, Lombardini S, Boni MC, Fornaciari G, Sassatelli R, La Sala GB. Inflammatory bowel diseases and human reproduction: a comprehensive evidence-based review. World J Gastroenterol 2014; 20:7123-36. [PMID: 24966584 PMCID: PMC4064059 DOI: 10.3748/wjg.v20.i23.7123] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2013] [Revised: 02/13/2014] [Accepted: 02/26/2014] [Indexed: 02/06/2023] Open
Abstract
To evaluate the effects of inflammatory bowel diseases (IBDs) on human reproduction, we reviewed the current literature using a systematic search for published studies (articles and/or abstracts) without limits for English language. We searched on Medline (through PubMed), the Institute for Scientific Information, the Web of Science and the websites for the registration of controlled trials (http://controlled-trials.com/). Bibliographies of retrieved articles, books, expert opinion review articles and reviewed bibliographies from subject experts were manually searched. Titles and abstracts were screened initially, and potential relevant articles were identified and reviewed. Whenever possible, data were analyzed by comparing IBD patients vs healthy controls, and patients with active IBDs vs those with disease in remission. The effects of IBDs on female fertility, fertility in infertile couples, pregnancy and male infertility were examined separately. Patients with IBDs in remission have normal fertility. At the moment, there is no established guideline for the preservation of fertility in women with IBD undergoing surgery. Further data are needed regarding guidelines for the management of these patients. Data regarding IBDs and infertility are currently completely lacking. Considering the prevalence of intestinal pathology in young adults of childbearing age, this field is of great scientific and clinical interest, opening up important future perspectives. Another important and as yet unexplored point is the response to treatments for infertility in patients with IBDs. In particular, the question is whether the reproductive outcomes (clinical and biological) can be influenced by the IBD of one of the partners. The goals for successful reproductive outcomes in IBD population are correct counseling and disease remission. IBDs significantly affect several reproductive aspects of human (female, male, couple) reproduction. Further data are needed to develop guidelines for the clinical management of subjects of reproductive age with IBDs.
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Chebli JMF, Gaburri PD, Chebli LA, da Rocha Ribeiro TC, Pinto ALT, Ambrogini O, Damião AOMC. A guide to prepare patients with inflammatory bowel diseases for anti-TNF-α therapy. Med Sci Monit 2014; 20:487-498. [PMID: 24667275 PMCID: PMC3972052 DOI: 10.12659/msm.890331] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2014] [Accepted: 01/21/2014] [Indexed: 12/22/2022] Open
Abstract
Current therapy of moderate-to-severe inflammatory bowel disease (IBD) often involves the use of anti-tumor necrosis factor alpha (TNF-α) agents. Although very effective, theses biologics place the patient at increased risk for developing infections and lymphomas, the latter especially when in combination with thiopurines. Appropriate patient selection, counseling, and education are all important features for the successful use of anti-TNF-α therapy. A thorough history to rule-out contraindications of this therapy and emphasis on monitoring guidelines are important steps preceding administration of anti-TNF-α agents. This therapy should only be considered if a recent evaluation has established that the patient has active IBD. In addition, it is important to exclude disease mimickers. Anti-TNF-α agents have been considered to present a globally favorable benefit/risk ratio. However, it is important that in routine practice, initiation of anti-TNF-α therapy be carefully discussed with the patient, extensively explaining the potential benefits and risks of such treatment. Prior to starting anti-TNF-α therapy, the patients need to be screened for latent tuberculosis, hepatitis B virus infection, and (usually) hepatitis C virus and HIV infection. Vaccination schedules of IBD patients should be evaluated and updated prior to the commencement of anti-TNF-α therapy. Ordinarily, immunization in adult patients with IBD should not deviate from recommended guidelines for the general population. With the exception of live vaccines, immunizations can be safely administered in patients with IBD, even those on immunosuppressants or biologics. The purpose of this review is providing an overview of appropriate steps to prepare patients with IBD for anti-TNF-α therapy.
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Affiliation(s)
- Júlio Maria Fonseca Chebli
- Division of Gastroenterology, Inflammatory Bowel Disease Center, Federal University of Juiz de Fora, Juiz de Fora, Brazil
| | - Pedro Duarte Gaburri
- Division of Gastroenterology, Inflammatory Bowel Disease Center, Federal University of Juiz de Fora, Juiz de Fora, Brazil
| | - Liliana Andrade Chebli
- Division of Gastroenterology, Inflammatory Bowel Disease Center, Federal University of Juiz de Fora, Juiz de Fora, Brazil
| | | | - André Luiz Tavares Pinto
- Division of Gastroenterology, Inflammatory Bowel Disease Center, Federal University of Juiz de Fora, Juiz de Fora, Brazil
| | - Orlando Ambrogini
- Division of Gastroenterology, Federal University of São Paulo (UNIFESP), School of Medicine, São Paulo, Brazil
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Abstract
This article provides an overview of the obstetric and gynecological manifestations of Crohn's disease (CD). High incidence of the new onset of the disease in young women in their reproductive years demands special concern from physicians involved in their treatment. Pregnant women with CD are considered high-risk patients, regardless of disease activity index, due to associated complications. Predominately described complications are premature birth, low birth weight, and congenital anomalies. To minimize the risk for adverse pregnancy/birth outcomes, it is recommended that remission be achieved before conception. Treatment of CD in pregnant women is similar to that among the nonpregnant population, and there is no valid reason to terminate it, since most of the drugs are proven to be safe. Women with CD who wish to conceive or are already pregnant need to be properly advised according to the newest guidelines on the subject, given by the European Crohn's and Colitis Organization. Gynecological manifestations are another special feature of CD. They are important in that they may facilitate early recognition of the underlying disease, which usually stays unrecognized for years before intestinal manifestation; in this way, the underlying manifestations are often mistreated.
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Affiliation(s)
- Ivana Plavšić
- Health Center, County of Primorje-Gorski Kotar, Rijeka, Croatia, Rijeka, Croatia
| | - Tea Štimac
- Department of Gynecology, Rijeka, Croatia
| | - Goran Hauser
- Department of Gastroenterology, Clinical Hospital Center Rijeka, Rijeka, Croatia
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Safety of anti-TNF agents during pregnancy and breastfeeding in women with inflammatory bowel disease. Am J Gastroenterol 2013; 108:1426-38. [PMID: 23752881 DOI: 10.1038/ajg.2013.171] [Citation(s) in RCA: 88] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2013] [Accepted: 04/30/2013] [Indexed: 02/08/2023]
Abstract
OBJECTIVES Anti-tumor necrosis factor (TNF) drugs are an effective therapeutic option in patients with inflammatory bowel disease (IBD). However, data regarding their safety during pregnancy and breastfeeding are scarce. The aim of this study was to critically review available data on the safety of anti-TNF therapy during pregnancy and breastfeeding in women with IBD. METHODS Bibliographical searches (MEDLINE) up to January 2013. RESULTS The studies included provided data from 462 women with IBD exposed to anti-TNF agents during pregnancy. Although these drugs cross the placenta from the end of the second trimester, they are low-risk in the short term. The use of anti-TNF agents after the second trimester leads to intra-uterine exposure. An increase in infections has recently been observed in infants exposed to immunomodulators plus anti-TNF drugs in utero, thus raising concerns about the consequences for the development of the immune system. Accordingly, it has recently been suggested that anti-TNF drugs should be stopped during the second trimester. Certolizumab is a Fab fragment of an anti-TNF monoclonal antibody, and, therefore, it may not be necessary to stop it during pregnancy. Anti-TNF drugs have been detected in breast milk, although in miniscule amounts. Case reports do not suggest toxicity; however, the effects of exposure on the neonate merit further investigation. CONCLUSIONS Anti-TNF drugs can cross the placenta from the latter part of the second trimester of gestation, although they seem to be safe, at least in the short term. Miniscule amounts of anti-TNF drugs are transferred in breast milk; therefore, a deleterious effect of this exposure on the neonate, although unlikely, cannot be excluded.
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Katz S. My treatment approach to the management of ulcerative colitis. Mayo Clin Proc 2013; 88:841-53. [PMID: 23910410 DOI: 10.1016/j.mayocp.2013.05.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2013] [Revised: 04/19/2013] [Accepted: 05/02/2013] [Indexed: 12/17/2022]
Abstract
Ulcerative colitis diagnosis and management represent a challenge for clinicians. The disguises of ischemia and acute infectious colitis continue to confound the diagnosis. The therapeutic options have remarkably expanded in the way of immunomodulators, biologics, or ileoanal pouch surgery, yet all carry potential considerable risks. These risks can confuse and impair patient acceptance, particularly elderly patients and men younger than 30 years. Predictors of outcome of medical and surgical therapy have improved but are far from complete. Nevertheless, therapies focused on the specific patient's condition continue to offer hope.
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Affiliation(s)
- Seymour Katz
- Department of Medicine, New York University School of Medicine, New York, NY; North Shore University Hospital-Long Island Jewish Health System, Manhasset, NY; and St Francis Hospital, Roslyn, NY.
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de Meij TGJ, Jharap B, Kneepkens CMF, van Bodegraven AA, de Boer NKH. Long-term follow-up of children exposed intrauterine to maternal thiopurine therapy during pregnancy in females with inflammatory bowel disease. Aliment Pharmacol Ther 2013; 38:38-43. [PMID: 23675854 DOI: 10.1111/apt.12334] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2013] [Revised: 04/03/2013] [Accepted: 04/24/2013] [Indexed: 12/23/2022]
Abstract
BACKGROUND Inflammatory bowel disease (IBD) affects a substantial number of female patients in their reproductive years. Therefore, many physicians face the dilemma whether thiopurines, prescribed to maintain remission, can be taken safely during pregnancy. Data on long-term development outcome of children exposed to maternal thiopurine therapy are very limited. AIM To assess the long-term effects of in utero exposure to thiopurines during pregnancy on infant health status. METHODS A prospective multicentre follow-up study was performed in children exposed intrauterine to maternal thiopurine therapy. Physical, cognitive and social aspects of infant health status were assessed with the 43-item TNO-AZL Preschool Children Quality of Life Questionnaire (TAPQOL). Furthermore, information on visits to general practitioner and medical specialists, and physician's advice regarding lactation was evaluated. Data were compared with normative data from a control group consisting of 340 children. RESULTS Thirty children were included in this study [median 3.8 years (IQR 2.9-4.7)]. No differences on global medical and psychosocial health status were found between children exposed to intrauterine thiopurines and the reference group. Exposure to intrauterine thiopurines was not associated with increased susceptibility to infection or immunodeficiency in childhood. Twenty-one of 30 children were exclusively formula-fed based on a negative advice of medical specialists directed at thiopurine use during lactation. CONCLUSIONS Thiopurine use during pregnancy did not affect long-term development or immune function of children up to 6 years of age. Our results underscore the present notion that mothers, even those using thiopurines, should be encouraged to breastfeed their infants.
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Affiliation(s)
- T G J de Meij
- Department of Pediatric Gastroenterology, VU University Medical Center, 1081 HV Amsterdam, The Netherlands.
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Flare up of ulcerative colitis during pregnancy treated by adsorptive granulocyte and monocyte apheresis: therapeutic outcomes in three pregnant patients. Arch Gynecol Obstet 2013; 288:341-7. [PMID: 23404436 DOI: 10.1007/s00404-013-2748-5] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2012] [Accepted: 01/29/2013] [Indexed: 02/07/2023]
Abstract
PURPOSE Treatment of ulcerative colitis with drugs during pregnancy potentially may harm the mother and the unborn child. Granulocytapheresis depletes elevated/activated myeloid lineage leucocytes as sources of inflammatory cytokines. We were interested in the safety and efficacy of granulocytapheresis in patients who had ulcerative colitis flare up during pregnancy. METHODS Three pregnant cases with active ulcerative colitis received Adacolumn granulocytapheresis, up to 10 sessions within 3-6 weeks. Case 1: a 33-year-old woman with left-sided colitis and bloody diarrhoea 7-9 times/day showed loss of mucosal vascular patterns, and contact bleeding from the rectum to the sigmoid colon. Case 2: a 36-year-old woman with pancolitis and bloody diarrhoea 6-8 times/day had loss of mucosal vascular patterns and pus from the rectum to the sigmoid colon. Case 3: a 36-year-old woman with pancolitis and diarrhoea 4-5 times/day (first episode) had erosions and pus in the mucosa from the rectum to the transverse colon. RESULTS Colitis flare was in weeks 5, 13 and 22 of pregnancy in cases 1, 2, 3, respectively. The corresponding granulocytapheresis sessions were 5, 7, and 10, reflecting an increasing trend with the pregnancy week. Patients 1 and 2 achieved complete remission, patient 3 achieved clinical remission. CONCLUSION In these three cases with active ulcerative colitis during pregnancy, granulocytapheresis as a non-pharmacologic treatment was effective and safe. In case 3 that did not respond well to the initial granulocytapheresis sessions, a moderate dose of prednisolone enhanced the efficacy of granulocytapheresis and tapering of prednisolone shortly after administration was not associated with relapse.
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Saha S, Wald A. Safety and efficacy of immunomodulators and biologics during pregnancy and lactation for the treatment of inflammatory bowel disease. Expert Opin Drug Saf 2012; 11:947-57. [PMID: 22954378 DOI: 10.1517/14740338.2012.720970] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
INTRODUCTION The inflammatory bowel diseases (IBD) are chronic, idiopathic, inflammatory conditions of the gastrointestinal tract, that peak in incidence during the reproductive years. Therefore, the safety of IBD medications during pregnancy and lactation is of significant interest to patients. Unfortunately, the current pregnancy labeling used by the United States Food and Drug Association (FDA) is often misinterpreted and may mislead healthcare providers and their patients to believe that risk increases from Category A to B to C to D to X, which in fact, is not the case. In addition, the FDA categories do not always distinguish between risks based on human versus animal data, or between differences in frequency, severity, and type of fetal developmental toxicities. AREAS COVERED This article provides an in-depth review of the available safety data during pregnancy and lactation for the more potent immunosuppressants used to treat IBD: the immunomodulators and biologics. It also includes the authors' expert opinions on the use of these medications during these critical periods. EXPERT OPINION The benefit-to-risk ratio for most immunomodulators and biologics used in the treatment of IBD favors medication continuation during pregnancy. Certain immunomodulators, however, can cause extreme fetal harm and should be used with caution. While human safety data regarding teratogenesis and some data on pregnancy outcomes exist for most IBD medications, long-term follow-up studies of children and young adults exposed to these drugs in utero are lacking. These studies are needed to determine if these drugs are of sufficiently low risk to be considered safe.
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Affiliation(s)
- Sumona Saha
- University of Wisconsin, School of Medicine and Public Health, 1685 Highland Avenue, Madison, 53705, USA
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